Mutations affecting the stability of the fushi tarazu protein of Drosophila.
We present a molecular analysis of four dominant alleles of the pair-rule gene ftz. Three of these, the ftzUal alleles, cause anti-ftz segmentation defects and homeotic transformations of the first abdominal segment to the third. These alleles are shown to be missense changes affecting two nearby proline codons. Embryos homozygous for these mutations accumulate higher levels of ftz protein than wild type and show strong persistence of ftz protein, but not RNA. These effects appear to result from stabilization of the ftz protein, since ftz stripes decay much more slowly in mutant embryos than in wild type after injection of the protein synthesis inhibitor cycloheximide. We trace the origin of segmentation defects in ftzUal embryos to repression of the pair-rule gene even-skipped by excess ftz protein during stripe sharpening. Homeotic transformations are shown to be correlated with ectopic expression of the abd-A gene of the bithorax complex. A 12-amino-acid sequence containing the proline residues altered in the ftzUal mutants appears to be conserved in the proteins encoded by other segmentation genes and the vertebrate oncogene myc and may target these proteins for rapid degradation. The fourth allele examined, T(2;3)ftzRpl(Rpl), also causes homeotic transformations and is a translocation broken within the ftz-coding region. Both ftz transcript and protein stripes are persistent in Rpl embryos, suggesting that the Rpl RNA is stabilized relative to wild type.
Kellerman
K A
KA
Department of Biology, Washington University, St. Louis, Missouri 63130.
Mattson
D M
DM
Duncan
I
I
D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal; D001483:Base Sequence; D003513:Cycloheximide / Q000494:pharmacology; D004330:Drosophila / Q000196:embryology / Q000235:genetics*; D029721:Drosophila Proteins; D004625:Embryo, Nonmammalian / Q000187:drug effects / Q000502:physiology; D051717:Fushi Tarazu Transcription Factors; D005799:Genes, Dominant; D006207:Half-Life; D018398:Homeodomain Proteins; D007301:Insect Hormones / Q000235:genetics* / Q000378:metabolism; D007700:Kinetics; D008969:Molecular Sequence Data; D009154:Mutation; D009693:Nucleic Acid Hybridization; D012689:Sequence Homology, Nucleic Acid; D014158:Transcription, Genetic
D000911:Antibodies, Monoclonal; D029721:Drosophila Proteins; D051717:Fushi Tarazu Transcription Factors; D018398:Homeodomain Proteins; D007301:Insect Hormones; C497169:ftz protein, Drosophila; D003513:Cycloheximide